Staphylococcus aureus (SA) is an opportunistic pathogen that can cause a wide spectrum of infections from superficial local skin infections to life-threatening systemic infections that can affect internal organs and tissues. In addition, bacterial arthritis, as well as acute and chronic osteomyelitis caused by haematogenous spread or by direct inoculation in open trauma or surgical intervention such as internal fixation or joint replacement, affect hundreds of thousands of patients each year (1–6). SA is also a major cause of infections associated with indwelling medical devices, such as catheters and prosthesis (6). The cost to society in patient care, which often involves extended hospital stays and repeated surgery, can be estimated at several billion dollars per year. With the documented emergence of multidrug resistance SA strains, the threat of this widely distributed pathogen is now appreciated and novel therapies for treatment and prevention are needed.
The successful colonization of the host is a process required for most microorganisms, including S. aureus, to cause infections in animals and humans. Microbial adhesion is the first crucial step in a series of events that can eventually lead to disease. Pathogenic microorganisms colonize the host by attaching to host tissues or serum conditioned implanted biomaterials, such as catheters, artificial joints, and vascular grafts, through specific adhesins present on the surface of the bacteria. MSCRAMM™S (Microbial Surface Components Recognizing Adhesive Matrix Molecules) are a family of cell surface adhesins that recognize and specifically bind to distinct components in the host's extracellular matrix. Once the bacteria have successfully adhered and colonized host tissues, their physiology is dramatically altered and damaging components such as toxins and proteolytic enzymes are secreted. Moreover, adherent bacteria often produce a biofilm and quickly become more resistant to the killing effect of most antibiotics.
S. aureus is thus known to express a repertoire of different MSCRAMM™S that can act individually or in concert to facilitate microbial adhesion to specific host tissue components. A search for such MCSRAMM's which recognized host components uncovered a 72-kDa protein identified as the major histocompatibility complex class II analog protein, or “Map” protein, a surface localized protein expressed by virtually every S. aureus strain (7). Cloning and sequencing of the gene encoding the Map protein revealed a protein consisting of roughly 110-amino acid-long domains repeated six times with each domain containing a 31 amino acid-long subdomain with homology to MHC Class II. If conservative amino acid substitutions were included, the respective subdomains were 61, 65, 52, 59, 52 and 45% similar to the amino-terminal end of the b chain of many MHC class II proteins from different mammalian species (8).
However, previous studies varied with regard to how the Map protein affected immune function, and thus it would be highly desirable to utilize the Map protein so as to affect the T cell immune responses in cases where pathogenic conditions result from a proliferation of T cells.